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Objectives: A self-constructed valved pulmonary conduit made out of a de-cellularized porcine small intestinal submucosal extracellular matrix biological scaffold was tested in a chronic growing lamb model. Methods: The conduit was implanted in pulmonary valve position in 19 lambs. We monitored clinical, laboratory, and echocardiographic findings until 12 months after surgery. In two animals, euthanasia was planned at nine and twelve months. Pre-mortem chest computed tomography and post-mortem pathologic work up were performed. Data are presented as frequency and percentage, median and range, or mean and standard deviation. Results: Twelve (63.2%) animals survived the perioperative period. Three unexpected deaths occurred during the follow-up period: one due to aspiration pneumonia at 23 days after surgery, and two due to early and late infective endocarditis of the conduit at 18 and 256 days. In the two animals with planned scarification, the pre-mortem CT scan revealed mild or no calcification within the conduit or valve leaflets. In the echocardiographic examination at 12 months, peak and mean systolic pressure gradients across the conduit valve were 6.5 (3–21) mmHg and 3 (2–12) mmHg, while valve regurgitation was none (n = 2), trivial (n = 5), moderate (n = 1), or severe (n = 1). No clinical or laboratory signs of hemolysis were seen. After 12 months of follow-up, the animals’ body weights had increased from 33 (27–38) kg to 53 (38–66) kg (p = 0.010). Conclusions: Implantation of a valved pulmonary conduit in our growing lamb model was feasible. Infective endocarditis of the implanted valved conduit remained a significant complication.

We developed a handmade expanded polytetrafluoroethylene (ePTFE) pulmonary valvular conduit (PVC) with bulging sinuses and a fan-shaped ePTFE valve for right ventricular outflow tract (RVOT) reconstruction. We aimed to investigate the results of this device in this multicenter study. From 2001 to 2020, 1776 patients underwent RVOT reconstruction using ePTFE PVCs at 65 institutions in Japan. The median age and body weight were 4.1 years (range, 3 days to 67.1 years) and 13.3 (range, 1.8-91.3) kg, respectively. The median PVC size was 18 (range, 8-24) mm. The median Z-value of the ePTFE PVC was 1.1 (range, -3.8 to 5.0). The ePTFE PVC conditions were investigated by cardiac echocardiography and catheterization. The median follow-up period was 3.3 years (range, 0 day to 16.2 years). There were only 9 cases (0.5%) with PVC-related unknown deaths. Reintervention was performed in 283 patients (15.9%), and 190 patients (10.7%) required explantation. Freedom from reintervention and explantation at 5/10 years were 86.7/61.5% and 93.0/69.1%, respectively. At the latest echocardiography, PVC regurgitation grade was better than mild in 88.4% patients. The average peak RVOT gradient was 15.7 ± 15.9 mm Hg at the latest cardiac catheterization. ePTFE PVC infection was detected in only 8 patients (0.5%). Relative stenosis due to somatic growth was the most common cause of PVC explantation. The performance of ePTFE in terms of durability, valvular performance, and the resistance against infection is considerable and may replace conventional prosthetic materials. Further improvement of the ePTFE membrane is essential to prevent valvular dysfunction. [ABSTRACT FROM AUTHOR]

To prepare a tissue‐engineered pulmonary valved conduit (PVC) with good tensile strength and biocompatibility. Sixty adult porcine PVCs were used to determine the optimal decellularization time. Five juvenile porcine decellularized PVCs and five juvenile porcine crosslinked PVCs were subsequently prepared according to the optimized decellularization and crosslinking methods. All PVCs were implanted into juvenile sheep for 8 months and then were harvested for staining. With a low concentration of detergent (0.25% Triton X‐100+0.25% sodium deoxycholate), the decellularization effect on porcine PVCs was complete by 24 hours, and there was minimal damage to the matrix. Gelatin embedding and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC) crosslinking improved the biomechanical properties of decellularized PVCs and reduced their immunogenicity. After implantation, the diameter and thickness of the PVCs in the decellularized and crosslinked groups increased significantly. In both groups, the conduits were unobstructed, with soft and smooth inner walls and without thrombosis, ulceration or neoplasia. The valves slightly degenerated with mild to moderate regurgitation. CD31‐positive endothelial cells were visible on the inner surface of the conduits and valves. Scattered smooth muscle actin‐positive cells were found in the middle layer of the conduit. The percentage of CD4‐ and CD68‐positive cells and the calcium content were highest in decellularized porcine PVCs and lowest in ovine PVCs. The percentage of the matrix that was laminin‐positive in decellularized and crosslinked porcine PVCs was lower than it was in ovine PVCs. Gelatin‐embedded and EDC‐crosslinked porcine PVCs can be "hosted" in sheep, with good biocompatibility, growth potential, and reduced calcification. [ABSTRACT FROM AUTHOR]

Objectives: We report the first use of a biorestorative valved conduit (Xeltis pulmonary valve–XPV) in children. Based on early follow-up data the valve design was modified; we report on the comparative performance of the two designs at 12 months post-implantation.Methods: Twelve children (six male) median age 5 (2 to 12) years and weight 17 (10 to 43) kg, had implantation of the first XPV valve design (XPV-1, group 1; 16 mm (n = 5), and 18 mm (n = 7). All had had previous surgery. Based on XPV performance at 12 months, the leaflet design was modified and an additional six children (five male) with complex malformations, median age 5 (3 to 9) years, and weight 21 (14 to 29) kg underwent implantation of the new XPV (XPV-2, group 2; 18 mm in all). For both subgroups, the 12 month clinical and echocardiographic outcomes were compared.Results: All patients in both groups have completed 12 months of follow-up. All are in NYHA functional class I. Seventeen of the 18 conduits have shown no evidence of progressive stenosis, dilation or aneurysm formation. Residual gradients of >40 mm Hg were observed in three patients in group 1 due to kinking of the conduit (n = 1), and peripheral stenosis of the branch pulmonary arteries (n = 2). In group 2, one patient developed rapidly progressive stenosis of the proximal conduit anastomosis, requiring conduit replacement. Five patients in group 1 developed severe pulmonary valve regurgitation (PI) due to prolapse of valve leaflet. In contrast, only one patient in group 2 developed more than mild PI at 12 months, which was not related to leaflet prolapse.Conclusions: The XPV, a biorestorative valved conduit, demonstrated promising early clinical outcomes in humans with 17 of 18 patients being free of reintervention at 1 year. Early onset PI seen in the XPV-1 version seems to have been corrected in the XPV-2, which has led to the approval of an FDA clinical trial.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02700100 and NCT03022708.

Objectives : A self-constructed valved pulmonary conduit made out of a de-cellularized porcine small intestinal submucosal extracellular matrix biological scaffold was tested in a chronic growing lamb model. Methods : The conduit was implanted in pulmonary valve position in 19 lambs. We monitored clinical, laboratory, and echocardiographic findings until 12 months after surgery. In two animals, euthanasia was planned at nine and twelve months. Pre-mortem chest computed tomography and post-mortem pathologic work up were performed. Data are presented as frequency and percentage, median and range, or mean and standard deviation. Results : Twelve (63.2%) animals survived the perioperative period. Three unexpected deaths occurred during the follow-up period: one due to aspiration pneumonia at 23 days after surgery, and two due to early and late infective endocarditis of the conduit at 18 and 256 days. In the two animals with planned scarification, the pre-mortem CT scan revealed mild or no calcification within the conduit or valve leaflets. In the echocardiographic examination at 12 months, peak and mean systolic pressure gradients across the conduit valve were 6.5 (3-21) mmHg and 3 (2-12) mmHg, while valve regurgitation was none (n = 2), trivial (n = 5), moderate (n = 1), or severe (n = 1). No clinical or laboratory signs of hemolysis were seen. After 12 months of follow-up, the animals' body weights had increased from 33 (27-38) kg to 53 (38-66) kg ( p = 0.010). Conclusions : Implantation of a valved pulmonary conduit in our growing lamb model was feasible. Infective endocarditis of the implanted valved conduit remained a significant complication.

Immunologically untreated frozen-stored xenografts show controlled rejection and repair due to reduced cellularity in our previous study. To clarify the issue, we compared results obtained using fresh and frozen-stored xenografts. Porcine pulmonary valved conduits were prepared without immunologic treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass immediately after harvest without frozen storage (the fresh group) or after frozen storage (−70°C for 3∼7 days) (the frozen group). Four goats were assigned to be raised for 3 ( N = 1) or 6 ( N = 3) months postoperatively in each group. One goat in the frozen group assigned for the 6-month observation expired at 2 months postoperatively because of thrombotic occlusion of the pulmonary valve. The other goats survived until the scheduled sacrifice. According to echocardiographic findings, one animal sacrificed at 3 months in the frozen group showed more than a moderate degree of pulmonary regurgitation, but all animals in the fresh group showed less than a mild degree. On gross examination, leaflets were slightly better preserved in the fresh group and aneurysmal dilatation of the pulmonary artery was observed at 3 months only in the frozen group. Microscopically, pulmonary arteries showed less severe degenerative changes in the fresh group. Moreover, in the fresh group, viable donor valve cells were still present until 3 months postoperatively (though it disappeared at 6 months postoperatively) and a linear endothelial lining of viable host cells was prominent on all leaflets, whereas this was not the case in the frozen group. In conclusion, fresh xenografts preserved cellular viability and showed fewer degenerative changes than frozen-stored xenografts. Thus, immunologically untreated fresh xenografts could provide a potential valve substitute with distinctive advantages in terms of self-healing potential as compared with frozen-stored xenografts. [ABSTRACT FROM AUTHOR]

This study was performed to evaluate the clinical feasibility of use of immunologically nontreated xenogenic valves, using a porcine-to-goat pulmonary valved conduit implantation model. Porcine pulmonary valve conduits were prepared with no specific immunological treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were assigned at predetermined intervals (1 day, 1 week, and 3, 6, and 12 months) as two animals for each interval. Echocardiographic examinations of the valves were performed before sacrifice. Upon retrieving the xenograft specimens, they were inspected visually and microscopically. Ten of the 12 animals survived the predetermined observation periods. Variable degrees of pulmonary regurgitation were the main findings on echocardiographic evaluations. On gross examination of the explanted specimens, all leaflets, except in one animal that prematurely died, were fairly well preserved. They were slightly shortened but free of thrombosis or vegetation. Aneurysmal dilatations of the anterior wall of the implanted pulmonary artery were observed in one of 12-month-survival animals and in another one of 3-month-survival animals. Microscopically, the three components of implanted xenografts (the pulmonary artery, valve, and infundibulum) were shown to be gradually replaced with host cells in time, while maintaining structural integrity. The nuclei of the donor tissue disappeared through pyknosis and karyolysis. In conclusion, immnunologically untreated xenogenic pulmonary valved conduits can be an alternative potential as valve substitutes with distinctive advantages of providing self-healing potential, despite a few problems observed in the current study such as occurrences of pulmonary regurgitation and sporadic cases of aortic aneurysm. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Since 1985, we have implanted handmade tri-leaflet conduits made of heterologous pericardium or expanded polytetrafluoroethylene (ePTFE), as an alternative to homograft for right ventricular outflow tract reconstruction. This report assesses the long-term outcome of these prostheses. Methods: From 1985 to 2003, 216 handmade tri-leaflet conduits were implanted in 191 patients. Forty-two patients had previous conduit repairs. The mean age at operation was 8.1±7.7 years (range: 15 days–44 years). The underlying diagnoses were pulmonary atresia with ventricular septal defect in 83 patients, atrioventricular discordance in 36, transposition of the great arteries in 26, double outlet right ventricle in 14, and truncus arteriosus in 17. Whole heterologous pericardial tri-leaflet conduits were implanted in 169 patients, in the early series (porcine: 85; equine: 58; bovine: 26); bovine pericardial conduits containing ePTFE leaflets were implanted in 26 patients since 1996; whole ePTFE tri-leaflet rolls were employed in the most recent 21 patients. The conduit size was 21.1±3.1mm (range: 12–27mm), 147.4±21.4% (range: 82.6–202.6%) of the anticipated diameter of the pulmonary valve. Follow-up was complete. Results: There were 28 early deaths and 24 late deaths. The indication for conduit replacement was a peak instantaneous pressure gradient of greater than 50mmHg. Sixty-five conduits required reoperation for conduit obstruction at 8.6±3.3 years after implantation. The freedom from reoperation at 5, 10, and 15 years was 93.9±1.9, 61.4±4.5, and 35.5±5.6%, respectively. Patients with smaller conduit size and young age at operation were predisposed to reoperation. None of the 47 ePTFE tri-leaflet conduits developed significant obstruction. The freedom from important pulmonary valve regurgitation (PR) as assessed by echocardiography was 68.3±3.7% at 5 years, 33.0±4.5% at 10 years, and 21.6±4.9% at 15 years. No patient required reoperation due to PR or right ventricular dysfunction. Conclusions: Handmade tri-leaflet conduits provide a reliable alternative for RVOT reconstruction in children, yielding as good a long-term outcome as do homografts. Longer follow-up is needed to determine how well ePTFE leaflets will fare. [Copyright &y& Elsevier]

Background: Pediatric right ventricular outflow tract (RVOT) reconstruction with homo- or porcine xenografts is problematic because of limited availability, lack of material for reconstruction, early degeneration, and tissue ingrowth. Contegra®, a bovine jugular vein graft, might be an interesting alternative to overcome these problems. Patients and methods: Within a Federal Drug Administration controlled study, we implanted 71 Contegra® pulmonary valved conduits from May 1999 to September 2001 in 71 patients (male/female 33/38) in the age range 2 days–17.4 years, median 1.2 years. Twenty five were primary repairs, 22 had previous graft implantations, and 24 had other repairs/palliations. Preoperative diagnoses: truncus arteriosus communis (19 patients), tetralogy of Fallot (32), double outlet right ventricle (13), transposition of the great arteries (5), and two rare complex malformations. The size of implanted Contegra® conduits ranged from 12 to 22 mm. Echocardiography was performed at 1 and 3 months, and then every 3 months postoperatively. Follow-up time was 27 months (maximal), 80 years in total. Results were compared with our 52 homograft- and 30 Tissuemed® porcine xenograft recipients. Results: Contegra® enables the surgeon to perform all anastomoses without additional material. Its tissue is very apt for suturing and its insufficiencies are common, but without clinical significance or tendency to increase. We saw no sign of conduit or valve degeneration during the whole follow-up up to 27 months. There were no device related adverse events. Redos: five for peripheral pulmonary arteries, two residual ventricular septum defect (VSD) closures. There were six deaths (five early, one late). The maximal transvalvular gradients of 25–42 mmHg were measured in seven patients; these gradients did not increase further during the follow-up. Six patients with completely intact Contegra® conduits developed pressure gradients of more than 70 mmHg immediately distal from the conduit. At 27 months, Contegra® grafts were advantageous compared to homografts with respect to survival and freedom from explantation. Right ventricle to left ventricle (RV/LV) ratio development and freedom from explantation/redo were equal for Contegra® conduits and homografts. Porcine Tissuemed® xenografts were significantly inferior. Conclusion: The Contegra® conduit offers unique tailoring and suturing options for primary and redo RVOT reconstruction. At 27 months, its durability seems at least equivalent to homografts and is superior to porcine Tissuemed® xenografts. [Copyright &y& Elsevier]

A case of aneurysm of the right ventricular outflow tract is described after repair of tetralogy of Fallot using a Contegra supported conduit. Angiograms revealed that the aneurysm was located between the ventricular anastomosis and the proximal ring of the conduit confirming echocardiographic data. Because the conduit between the rings was not dilated, the valve was perfectly functioning. Pulmonary anastomosis was severely stenosed explaining the dilatation seen below. Conduit replacement with resection of the aneurysmal part of the failing conduit was performed. Supported conduits do not eliminate the risk of secondary dilatation below the artificial ring but preserve valvular function. [Copyright &y& Elsevier]

Background: Many valvular pathologies of the heart may be only sufficiently treated by replacement of the valve if a reconstruction is not feasible. However, structural deterioration, thrombosis with thromboembolic events and infective endocarditis are commonly encountered complications over time and often demand a re-operation. In congenital heart disease the lack of small diameter valves with the potential to grow poses additional challenges and limits treatment options to homo- or xenograft implants., Methods: In this study, a chronic sheep model (24 months follow-up), a self-constructed valved conduit was created out of a tissue engineered (TE) patch (CorMatrix® Cardiovascular, Inc, USA) and implanted in orthotopic right ventricular (RV)-pulmonary artery (PA) position. Thereafter, the sheep were regularly monitored by clinical, laboratory and echocardiographic examinations to evaluate cardiac function and the implanted RV-PA-conduit., Discussion: Here, we summarize the study protocol and our experiences during the perioperative phase and the follow up period and explain how we constructed a valved conduit out of a commercially available TE patch., Trial Registration: License number: ZH 284/14., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)